Image-guided, Lobe-specific Hydrodynamic Gene Delivery to Swine Liver
Image-guided, Lobe-specific Hydrodynamic Gene Delivery to Swine Liver
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DOI：
10.1038/mt.2008.294
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发表时间：
2009-03-01
影响因子：
12.4
通讯作者：
Liu, Dexi
中科院分区：
文献类型：
--
作者：
Kamimura, Kenya;Suda, Takeshi;Liu, Dexi
在猪的肝脏中评估了图像引导，叶特异性流体动力学基因传递。手术过程包括在图像引导下将球囊导管从颈静脉插入选定肝叶的肝静脉，并使用新开发的计算机控制注射装置进行质粒DNA的流体动力学注射。我们证明了手术的影响是区域性的，对邻近的脑叶影响最小。注射pCMV-Luc质粒4小时后，靶叶的基因表达水平为10(7)相对光单位(RLU)/mg，非靶叶的基因表达水平为10(2)-10(5)相对光单位/mg。阻断下腔静脉（IVC）或IVC +门静脉（PV）的血流可有效提高目标血管的动水压力，但不能提高基因传递效率。下腔静脉闭塞猪的生理检查显示血压和呼吸速率一过性降低。移除下腔静脉阻塞导致心率快速和短暂的增加。PV和肝静脉的闭塞对生理和心脏活动没有影响。血清成分未见明显变化。这些结果表明：(1)图像引导的，特定于肺叶的流体动力程序对肝脏区域基因传递是有效的，(2)流体动力基因传递到肝脏应避免静脉阻塞，(3)流体动力基因传递到肝脏的临床应用是可行的。
Image-guided, lobe-specific hydrodynamic gene delivery to liver was assessed in pigs. The procedure involved image-guided insertion of a balloon catheter to the hepatic vein of the selected lobe from the jugular vein and hydrodynamic injection of plasmid DNA using a newly developed computer-controlled injection device. We demonstrated that the impact of the procedure was regional with minimal effects on neighboring lobes. Level of gene expression resulted from the procedure was 10(7) relative light units (RLU)/mg in the targeted lobes and 10(2)-10(5) RLU/mg in the nontargeted lobes 4 hours after hydrodynamic injection of pCMV-Luc plasmids. Occlusion of blood flow in the inferior vena cava (IVC) or IVC plus portal vein (PV) was effective in elevating hydrodynamic pressure in the targeted vasculature but did not enhance gene delivery efficiency. Physiological examination on pigs with IVC occlusion revealed transient decreases of blood pressure and respiration rate. Removal of occlusion from IVC resulted in a rapid and transient increase in heart rate. Occlusion of the PV and hepatic vein showed no effect on physiological and cardiac activities. No major changes in serum composition were observed. These results suggest that (i) image-guided, lobe-specific hydrodynamic procedure is effective for regional gene delivery to liver, (ii) blockade in IVC should be avoided for hydrodynamic gene delivery to the liver, and (iii) clinical application of hydrodynamic gene delivery to liver is feasible.